Personalizing Stem Cell Research and Therapy: The Arduous Road Ahead or Missed Opportunity?

Abstract

The euphoria of stem cell therapy has diminished, allowing scientists, clinicians and the general public to seriously re-examine how and what types of stem cells would effectively repair damaged tissue, prevent further tissue damage and/or replace lost cells. Importantly, there is a growing recognition that there are substantial person-to-person differences in the outcome of stem cell therapy. Even though the small molecule pharmaceuticals have long remained a primary focus of the personalized medicine research, individualized or targeted use of stem cells to suit a particular individual could help forecast potential failures of the therapy or identify, early on, the individuals who might benefit from stem cell interventions. This would however demand collaboration among several specialties such as pharmacology, immunology, genomics and transplantation medicine. Such transdisciplinary work could also inform how best to achieve efficient and predictable stem cell migration to sites of tissue damage, thereby facilitating tissue repair. This paper discusses the possibility of polarizing immune responses to rationalize and individualize therapy with stem cell interventions, since generalized "one-size-fits-all" therapy is difficult to achieve in the face of the diverse complexities posed by stem cell biology. We also present the challenges to stem cell delivery in the context of the host related factors. Although we focus on the mesenchymal stem cells in this paper, the overarching rationale can be extrapolated to other types of stem cells as well. Hence, the broader purpose of this paper is to initiate a dialogue within the personalized medicine community by expanding the scope of inquiry in the field from pharmaceuticals to stem cells and related cellbased health interventions.

Stem cell culture engineering – process scale up and beyond

“…For those applications, the source of the cells will be a major hurdle because the cells should be healthy and may need to be isolated before the disease state of the patient. These patient‐derived stem cells might be susceptible to contamination, genetic modifications, or might already possess disease‐causing mutations that are not apparent at the time of transplantation, thereby compromising the outcome of therapy 35. Such applications will pose a challenge, even from a process perspective.…”

Personalized cardiac regeneration by stem cells–Hype or hope?

“…Autologous transplantations employ a patients own tissue and thus present no tissue incompatibility between the donor and the host due to a lack of stimulation of the immune response. However, in cases where there is a need for immediate treatment with stem cells, it will not be practical to wait for ex vivo expansion and re-transplantation of autologous stem cells [30]. Moreover, because the functional impairment of stem and progenitor-derived cells harvested from patients with chronic heart failure may limit the efficiency of autologous stem cell treatment.…”

“…Several humoral factors govern and control these processes [36]. Thus variations among microenvironments which could be influenced by the patient’s background as well as other underlying clinical disorders might be relevant for the functions of stem cells in each different host [30]. The composition of the microenvironment and the presence of certain soluble factors are major determinants for proliferation, differentiation and homing of applied stem or progenitor cells.…”

“…Ultimately, personalization of health interventions, such as cell-based therapies, rests on a firm understanding of the mechanisms of person to person variations in treatment outcomes. Future studies to enhance the identification of molecular differences will allow a fundamental redefinition of diseases at the molecular and cellular levels and enable identification of patients with similar characteristics to estimate the outcome of treatment strategies [30, 72]. The heterogeneity among patient factors and the biology of different stem cell types merits the need for personalized approach to stem cell therapy and other cell-based treatments.…”

Human Amniotic Mesenchymal Stem Cell-Derived Induced Pluripotent Stem Cells May Generate a Universal Source of Cardiac Cells

“…To address this issue, autologous iPSCs derived from the patient's somatic cells are considered a potentially landmark solution. Even in a situation where an immediate treatment is unnecessary, a therapeutic strategy to wait for ex vivo reprogramming and expansion with the subsequent retransplantation of autologous stem cells may not be financially and clinically feasible [28]. Recently, Zhao et al reported that the cells differentiated from iPSCs can induce Tcell-dependent immune responses in syngeneic recipients [29].…”